Hyperhomocysteinemia: a trigger for complement-mediated TMA?
Acta Clin Belg
; 76(1): 65-69, 2021 Feb.
Article
de En
| MEDLINE
| ID: mdl-31401947
ABSTRACT
A 34-year-old man of North African descent was referred to the emergency department because of malignant hypertension (220/113 mmHg), acute visual disturbances and acute kidney failure (serum creatinine 14.0 mg/dL). Blood analysis was compatible with thrombotic microangiopathy (TMA). Kidney biopsy confirmed this diagnosis with histological changes including intimal edema, arteriolar thrombi, and severe tubulointerstitial damage. Fundoscopy showed hypertensive retinopathy stage IV. Subsequent biochemical screening revealed normal complement testing and a marked elevation in homocysteine concentration (161 µmol/L; normal value 7-15 µmol/L). Other secondary causes of TMA were excluded. Further genetic testing for cobalamin C (cblC) deficiency showed no pathogenic mutations in the MMACHC gene. However, a homozygous c.665C>T polymorphism (NM_005957.4) in the methylenetetrahydrofolate reductase (MTHFR) gene was found explaining the severe hyperhomocysteinemia due to reduced activity of MTHFR. Additional genetic testing for alternative complement pathway proteins showed mutations in the genes encoding factor H and factor B, both categorized as possibly pathogenic using mutation prediction software. This is the first described case of TMA in a patient with severe hyperhomocysteinemia caused by a genetic defect other than cblC. We postulate that endothelial damage due to hyperhomocysteinemia and hypertension could have triggered the TMA episode in this patient with two possible predisposing pathogenic mutations in the alternative complement pathway. Furthermore, our case demonstrates the need for complete full diagnostic testing in patients with TMA.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Hyperhomocystéinémie
/
Microangiopathies thrombotiques
Type d'étude:
Diagnostic_studies
/
Etiology_studies
/
Prognostic_studies
Limites:
Adult
/
Humans
/
Male
Langue:
En
Journal:
Acta Clin Belg
Année:
2021
Type de document:
Article
Pays d'affiliation:
Belgique